Potassium channel expression in human CD4+ regulatory and naïve T cells from healthy subjects and multiple sclerosis patients

The membrane potential of human T cells is regulated by two potassium channels: the voltage-gated KV1.3 and the Ca2+-activated KCa3.1. These two channels are essential for efficient antigenic activation and proliferation of T cells and are expressed at different levels in naïve, central memory and effector memory T cells. This provides the opportunity to inhibit the proliferation of the targeted subtype by channel-specific blocking compounds. Regulatory T cells (Tregs) also represent a unique subtype of T cells that perform highly specialized tasks in controlling immune responses, which raises the possibility that they too have a distinctive channel expression pattern. Using whole-cell patch-clamp we tested this hypothesis and determined the ion channel expression of CD4+CD25hiCD127lo regulatory and CD4+CD25loCD127hi naïve T cells from the peripheral blood of healthy volunteers and multiple sclerosis (MS) patients sorted by flow cytometry. We have found that naïve and Treg cells from healthy controls expressed equal numbers of KV1.3 channels, while Tregs had a greater membrane surface as assessed by capacitance measurements, and consequentially lower channel density than naïve cells, indicating an “incomplete activation state” of Tregs. In contrast, Tregs from MS patients had fewer KV1.3 channels than naïve cells and there was no difference in the membrane capacitance or channel density between the two subtypes of cells. The expression level of KCa3.1 channels was similar in all cell subsets. The observed differences in KV1.3 channel expression density may contribute to the varying responses upon antigenic stimulation by these cell types in health and disease.